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February 18, 2014
08:13 EDTMACKMerrimack MM-141 preclinical study published in Molecular Cancer Therapeutics
Merrimack Pharmaceuticals announced that the manuscript "MM-141, an IGF-1R- and ErbB3-Directed Bispecific Antibody, Overcomes Network Adaptations That Limit Activity of IGF-1R Inhibitors" has been published in Molecular Cancer Therapeutics and selected for the Highlights section in the current issue . This publication describes the preclinical development of Merrimack's MM-141, a novel bispecific tetravalent antibody that binds to IGF-1R and ErbB3 receptors. With this mechanism, MM-141 is able to inhibit oncogenic signaling through the PI3K/AKT/mTOR pathway, which is a driving force behind cell growth. MM-141 recently completed the monotherapy portion of a Phase 1 study in the United States and Europe. It is currently being investigated in a Phase 1 combination study and is expected to enter Phase 2 development in 2014. IGF-1R, the receptor activated by insulin-like growth factor 1, has the ability to induce cellular growth and proliferation. Thus, it has been implicated in promoting resistance to both chemotherapies and targeted therapies. However, the effectiveness of current IGF-1R inhibitors in the clinic has been limited, as cancer cells have the ability to develop resistance to therapies by signaling through alternative pathways. Through a systems biology-based methodology, Merrimack researchers have found that cancer cells can develop resistance to IGF-1R that is mediated through ErbB3. Therefore, dual inhibition of IGF-1R and ErbB3 pathways would be necessary to block the PI3K/AKT/mTOR pathway, resulting in the arrest of tumor cell growth. In preclinical in vitro and in vivo models, MM-141 was more active than a combination of anti-ErbB3 and anti-IGF-1R monoclonal antibodies. MM-141 was able to inhibit PI3K/AKT/mTOR signaling and potentiated the activity of cytotoxic and targeted therapies, supporting its ongoing clinical development.
News For MACK From The Last 14 Days
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April 28, 2015
05:09 EDTMACKMerrimack completes MM-398 NDA submission to FDA
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April 27, 2015
07:04 EDTMACKMerrimack and Baxter complete submission of NDA for MM-398
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April 21, 2015
09:22 EDTMACKOn The Fly: Pre-market Movers
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08:10 EDTMACKMerrimack to present updated clinical data from Phase 1 study of MM-141
Merrimack Pharmaceuticals announced updated clinical data from a multi-arm Phase 1 study of MM-141, a bispecific antibody targeting IGF-1R and ErbB3. The data were presented in an oral session at the 2015 American Association for Cancer Research Annual Meeting in Philadelphia, PA. The trial evaluated the safety and tolerability of MM-141 as a monotherapy and in combination with everolimus or with nab-paclitaxel and gemcitabine in patients with advanced solid tumors.
06:01 EDTMACKMerrimack price target raised to $16 from $13 at Mizuho
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April 20, 2015
16:07 EDTMACKMerrimack announces final clinical results for MM-302 Phase 1 study
Merrimack Pharmaceuticals announced updated and final clinical results for the Phase 1 study of MM-302, a novel HER2-targeted liposomal doxorubicin, in HER2-positive metastatic breast cancer. Data described the safety and promising clinical activity of MM-302 in patients with advanced HER2-positive metastatic breast cancer. Results from the trial showed that the group of patients treated with 30 mg/m2 or more of MM-302 alone, in combination with trastuzumab or with trastuzumab and cyclophosphamide, had a median progression free survival, or mPFS, of 7.6 months and an overall response rate, or ORR, of 11%. Of note, 25 patients who had not been previously treated with anthracyclines had an mPFS of 11 months and an ORR of 24%. The most frequent adverse events occurring in greater than 20% of the population in this Phase 1 study were constipation, cough, decreased appetite, diarrhea, dyspnea, fatigue, nausea, neutropenia, stomatitis and vomiting. The most common Grade 3/4 adverse event was neutropenia observed in 8 patients. Six out of 69 patients 9% had protocol-defined asymptomatic declines in left ventricular ejection fraction, or LVEF. In 1 of the 6 patients, this was reported as a Grade 1 cardiac failure that was possibly related to study treatment. Merrimack is currently enrolling the HERMIONE study that is designed to support a potential application for accelerated approval in the U.S. and conditional marketing authorization in the E.U. The HERMIONE study is for HER2-positive, metastatic breast cancer patients who are anthracycline-naive and have not been previously treated with pertuzumab and T-DM1-containing regimens.
07:20 EDTMACKAmerican Association for Cancer Research to hold annual meeting
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April 14, 2015
09:17 EDTMACKMerrimack management to meet with Brean Capital
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